Effect of Genetic Polymorphism on the Clinical Outcome to SGLT2 Inhibitors in Heart Failure Patients

March 24, 2025 updated by: Neven Sarhan, Ain Shams University
Heart failure with reduced ejection fraction (HFrEF) is a significant cause of morbidity and mortality. Sodium-glucose co-transporter-2 (SGLT2) inhibitors have demonstrated efficacy in improving renal outcomes in patients with HFrEF. Pharmacogenetics, the study of how genetic variations influence drug response, could elucidate inter-individual variability in treatment outcomes. This study aims to assess the impact of specific genetic variants on renal outcomes in HFrEF patients treated with SGLT2 inhibitors.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

Heart failure is broadly classified into two main types based on the left ventricular ejection fraction (LVEF): heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF). HFpEF is characterized by a preserved or relatively normal LVEF, typically equal to or greater than 50%, despite signs and symptoms of heart failure. In contrast, HFrEF is defined by a reduced LVEF, typically less than or equal to 40%. [4] Accurate categorization of HF into HFpEF or HFrEF enables healthcare providers to implement targeted therapeutic approaches.

The intricate nature of heart failure necessitates a comprehensive approach to its diagnosis and management, given its varying presentations and underlying mechanisms. Heart injury, precipitated by diverse causes such as myocardial infarction, hypertension, and cardiomyopathies, triggers a complex and deleterious process of pathological remodeling and fibrosis within the cardiac tissue. This progressive cascade of events ultimately leads to the manifestation of heart failure. The pathophysiological mechanisms driving this progression are multifaceted, involving intricate cellular responses, neurohormonal activation, and inflammatory pathways. The initial insult, such as ischemic injury from myocardial infarction or chronic pressure overload from hypertension, sets in motion a series of maladaptive responses within the myocardium. These responses include cardiomyocyte hypertrophy, interstitial fibrosis, and alterations in extracellular matrix composition, which collectively impair myocardial contractility and promote ventricular dysfunction over time.

SGLT2 inhibitors, initially developed to manage blood glucose levels in patients with type 2 diabetes, now form part of the latest therapeutic strategies for heart failure as outlined in the 2022 AHA guidelines. This class, which includes empagliflozin, canagliflozin and dapagliflozin, has been shown to significantly reduce hospitalizations for heart failure and cardiovascular mortality in patients with symptomatic chronic HFrEF, irrespective of the presence of type 2 diabetes. Empagliflozin, a specific SGLT2I, has been particularly studied for its cardio-renal protective effects. Research by Miyata et al. (2021) has revealed that Empagliflozin goes beyond glycemic control by exerting beneficial effects on inflammatory and fibrotic markers.

Study Type

Observational

Enrollment (Estimated)

200

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Egypt
      • Cairo, Egypt, 11315
        • National Heart Institute

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Probability Sample

Study Population

Heart Failure patients with reduced ejection fraction (LVEF<40%)

Description

Inclusion Criteria:

  • Adults (≥18 years) with HFrEF (LVEF ≤40%).
  • Initiation of SGLT2 inhibitor therapy.
  • Stable background HF therapy for at least 4 weeks.
  • Written informed consent for participation and genetic testing.

Exclusion Criteria:

  • Known hypersensitivity to SGLT2 inhibitors.
  • History of ketoacidosis or recurrent urinary tract infections.
  • End-stage renal disease (eGFR <30 mL/min/1.73 m²).
  • Life expectancy <6 months due to non-cardiovascular conditions.
  • Pregnancy or lactation.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Cohort A
Newly diagnosed Heart Failure patients with reduced ejection fraction who are candidate for add-on treatment with sodium glucose transporter 2 inhibitor (SGLT2i) for the first time in addition to standard heart failure therapy.
Drug: SGLT2 inhibitor (Dapagliflozin 10mg)
Renal response after 6 months of Dapagliflozin therapy among patients with heart failure reduced ejection fraction.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Reno-protective effect and gene polymorphism
Time Frame: 6 months
Association between genetic polymorphism in SLC5A2, UMOD and ACE and Renal response in-terms of change in GFR among patients with heart failure.
6 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Gene polymorphisms and Renal biomarkers
Time Frame: 6 months
Association between genetic polymorphism in SLC5A2, UMOD and ACE and Renal biomarkers among patients with heart failure.
6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Ain Shams University

Collaborators

Misr International University
Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia
National Heart Institute in Egypt

Investigators

  • Study Chair: Bassem Zarif, MD, National Heart Institute

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 22, 2023

Primary Completion (Estimated)

June 1, 2025

Study Completion (Estimated)

July 1, 2025

Study Registration Dates

First Submitted

March 24, 2025

First Submitted That Met QC Criteria

March 24, 2025

First Posted (Actual)

March 30, 2025

Study Record Updates

Last Update Posted (Actual)

March 30, 2025

Last Update Submitted That Met QC Criteria

March 24, 2025

Last Verified

March 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SGLT2 INHIBITORS

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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